An epidemiologic cohort study of intravenous drug users (IVDUs) will be conducted with the aims of (1) investigating behavioral, clinical and immunologic events surrounding seroconversion to human immunodeficiency virus type 1 (HIV); (2) determining standardized mortality ratios (SMRs) by cause among HIV-infected and -uninfected IVDUs and investigating risk factors for significantly elevated causes of death via embedded case-control studies; (3) investigating the independent and interactive effects of HIV, hepatitis B virus (HBV), hepatitis C (HBC), hepatitis delta virus (HDV), and human T-cell lymphotropic virus type I (HTLV-I) on immunologic and clinical signs and symptoms; and (4) creating a serum and cell specimen bank to permit efficient study of issues related to AIDS, HIV, and other diseases among IVDUs. All members of the cohort will be seen every six months. More frequent contact, at least once each month, will be maintained with HIV-seronegative subjects whose drug-use or sexual practices place them at highest risk of HIV infection. In addition, persons experiencing symptoms suggestive of the acute HIV seroconversion syndrome will be recalled for examination, laboratory studies and interview. Statistical comparison of symptoms associated with HIV seroconversion syndrome with symptoms found in other mono-like illnesses will improve the ability to clinically diagnose HIV seroconversion. Risk factors for HIV seroconversion and for severe as contrasted to mild seroconversion symptoms will be analyzed. Immunologic variables to be measured and investigated for prognostic utility at seroconversion and thereafter include lymphocyte counts, CD4 percents, CD4 cell counts, CD8 counts, CD4/CD8 ratios, beta-2 microglobulin, and immunoglobulins G, A, and M. HIV tests to be conducted include enzyme-linked immunosorbent assay, western blot, p24 serum antigen, and, as appropriate, polymerase chain reaction. All subjects will be tested at each recall for exposure HBV and HTLV-1. Vital statistics follow-up of all subjects ever enlisted into the cohort study will be conducted annually to determine standardized mortality ratios by cause. Embedded case-control studies will then be used to analyze the importance of possible co-factors, including co-infection with HBV, HCV. HDV, and HTLV-1, for different causes of death, such as liver disease, neurologic disorders, or specific types of cancer. Statistical methods to be used include cluster analysis to identify patterns of symptoms associated with HIV seroconversion; Poisson regression to analyze risk factors for HIV seroconversion; Kaplan-Meier estimation, logistic regresssion, and Cox regression techniques to analyze prognostic factors for fast compared to slow immunologic decline, AIDS, and death.